Contrast-Enhanced Breast Tomosynthesis

Transcription

1 Contrast-Enhanced Breast Tomosynthesis AIP Industrial Physics Forum 2009 Andrew D. A. Maidment, Ph.D. Chief, Physics Section Department of Radiology University of Pennsylvania

2 Acknowledgements of Support Grant support from the Komen Foundation, DOD, NIH, RSNA, Hologic and XCounter AB. Dr. Maidment is a scientific advisor to the RTT and XCounter. Susan Ng Maidment is the President and CEO of RTT. FDA Statement This presentation will include off-label uses and applications and devices not yet approved for human use in the United States.

3 Digital Breast Mammography Tomosynthesis

4 Mammography and Tomosynthesis μ 1 μ 2 t a b a b M t o b t o a I I I I C e I I e I I + = = = 2 1 μ μ Contrast arises from different attenuation in various paths through an object

5 Mammography and Tomosynthesis

6 I = I 0 e μx

7 ln( I 0 I ) = μ x

8 ln( I 0 I) x = μ

9 ln( I 0 I) x = μ ln( I I) x = ~ μ 0

10 Vascular Contrast Enhancement Methods The development of an independent vasculature is an essential step in the development of a cancer A contrast agent should be able to demonstrate these vessels and the lesion itself

11 JL Yu, JW Rak, G Klement and RS Kerbel [Cancer Research 62, , March 15, 2002]

12 Vascular Contrast Enhancement Methods A variety of approaches have been investigated to elucidate tumor vasculature, including x-rays, tomosynthesis, CT, MRI and ultrasound Radiographic techniques are now readily achievable because of the prevalence of digital mammography, the emergence of digital breast tomosynthesis, and the high quantum efficiency and low detector noise of existing technology

13 Contrast-Enhanced Breast MR Today, MR is the most common breast imaging method to use vascular contrast agents MR is used to distinguish benign from malignant tissues on the basis of enhance, washout, temporal characteristics and morphology Tumors will rapidly take up the contrast agent, but it will wash out slowly

14 First Reports of Breast MRI: El Yousef et al: Radiology 1984 Stelling et al: Radiology 1985 Dash et al: AJR 1986 Contrast Enhanced Breast MRI: Kaiser et al: Radiology 1989 Heywang et al: Radiology 1989 Higher Resolution 3D Imaging: Harms et al: Radiology 1993 Orel et al: Radiology 1994 MRI Guided Bx: Schnall et al: RSNA 1993 Heywang et al: RSNA 1993 MRI of the Breast 2009 Courtesy M. Schnall U of PA 150 μm spatial resolution

15 Benign Fibroadenoma

16 Intraductal Carcinoma

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18 Current ACR MRI Recommendations A. Screening 1. High-Risk Patients 2. Contralateral breast of patients with new malignancies 3. Patients pre-augmentation and having free injection augmentation

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21 Current ACR MRI Recommendations B. Extent of Disease 4. Invasive and ductal carcinoma in situ 5. Invasion deep to fascia 6. Post lumpectomy with positive margins 7. Neoadjuvant chemotherapy Diagnostic imaging of all women with cancer prior to treatment % of women will have multifocal or multi-centric breast cancer.

22 Chemoprevention J. P. Delille et al., Radiology 235, 36 (2005).

23 Neoadjuvant Chemotherapy

24 Current ACR MRI Recommendations C. Additional Evaluation of Findings 8. Recurrence of Breast Cancer 9. Metastatic disease with unknown origin of primary 10.Lesion characterization 11.Post-operative reconstruction 12.MRI guided biopsy

25 Breast CT 100 ml (3 ml/s) intravenous injection Iopamiron 300 (Nihon Schering, Osaka) Scanned at 30s and 120s post-injection M Nishino et al, J CAT, 27(5),

26 Invasive IDC Invasive IDC Multiple Fibroadenomas Papilloma

27 Dedicated breast CT scanner pendant geometry Slide Courtesy John Boone, Ph.D.

28 PRE CONTRAST BCT SUBTRACTION IMAGES SUBTRACTION POST CONTRAST Pt 122

29 Contrast-Enhanced Digital Mammography The advent of modern digital mammography has led to a renewed interest in breast angiography. The field is now called contrast-enhanced digital mammography. Rather than image blood vessels, the desire is to fractionally increase the contrast of breast lesions by virtue of their slightly increased uptake and retention of contrast media as compared to surrounding tissue.

30 Temporal Subtraction In temporal subtraction angiography, an initial mask image is produced and stored prior to the injection of contrast material The contrast media is then injected Finally, a series of post-contrast images are acquired Subtracted images are produced by logarithmically subtracting the initial mask image from each of the post-contrast images

31 Temporal Subtraction Mass attenuation[cm 2 /g] ICRU-44 Breast Tissue Iodine 0.27 mm Cu Energy [kev] Photon Fluence [# photons/mm 2 ]

32 Jong and Yaffe 22 women with mammographic abnormalities underwent CE digital mammography. 6 images were obtained with contrast injected intravenously between the 1st and 2nd images. Enhancement was observed in 8 of 10 patients with cancer. In 2 cancer cases, no enhancement was observed. No enhancement was seen in seven of 12 benign cases, which were otherwise suspected as cancer. Lesion enhancement kinetics was similar to MRI. RA Jong, MJ. Yaffe, et al. Radiology 228: , 2003

33 CC 1 Min IDC IDC Papilloma Papilloma Courtesy M. Yaffe

34 Patient With Benign Lesion (Fibrocystic Change) Scout 1 min. 5 min. 30 Enhancement Kinetics Lesion Mean - Tissue Mean in Subtracted Images Time (minutes) Courtesy M. Yaffe

35 Infiltrating Ductal Carcinoma Scout 1 min. 7 min. 3 Kinetics mg/cm Time (minutes) Courtesy M. Yaffe

36 CE Tomosynthesis Method MLO projection with 5-7 dn compression X-ray tube 49 kvp, Rh target, 0.27 mm Cu filter 9 projections per data set: 50 o arc, 6.25 o apart 1 projection each 30 sec Dose per data set ~ mammogram (~2 mgy) 68 cm 20 cm Pivot point Compression plate Breast Detector

37 CE Tomosynthesis Method 1 ml/kg of Visipaque-320 (320 mg I/ml iodixanol) - Amersham, Princeton, NJ. 60 ml saline flush. First post-contrast image obtained 90 sec after start of contrast injection. Total exam time ~ 10 minutes. 17 patients to date

38 Patient 1: Digital Mammography Right breast cm ill-defined asymmetry overlying pectoralis muscle

39 Patient 1: MRI Pre Gd T1 FS Post Gd FS Post Gd - sub 1.3 cm enhancing mass at 12:00 in right breast.

40 Contrast-Enhanced Tomosynthesis Pre-contrast Post-contrast Subtraction Spiculated mass with rim enhancement.

41 Image Registration The registration algorithm is a multi-scale, globally smooth and locally affine. Before registration, pre- and post-contrast images are sampled and averaged to preserve original geometry while reducing computational time, and improving the per pixel signal-to-noise ratio.

42 Raw files (18) Sort Pre-contrast Images (9) Post-contrast Images (9) 2294x1914 Sample, Average, Register 2294x1914 Registered post-contrast Images (9) 256x256 Sample, Mask, Normalize intensities Log (pre-contrast) Log (post-contrast) (9) 1147x957 Subtraction Images (9) Write format 1147x957 Projection Images (9) 1147x957

43 Patient 1: Motion Correction 38 yo with ductal carcinoma demonstrating strong enhancement. Registration reduced motion artifacts in axilla and inferior breast, resulting in superior visualization of the lesion and vasculature. BEFORE AFTER

44 Patient 2: Motion Correction BEFORE AFTER AFTER 43 yo with segmental enhancement in upper half of breast, concordant with MRI. In the pre-registered image, the enhancement was not discernable from motion artifacts.

45 Temporal Subtraction Advantages: Superior separation of pre- and post-contrast images High kvp pre- and post- contrast images Reduced total dose Disadvantages: Motion Artifacts

46 Dual-Energy Imaging At diagnostic energies, there are two main x-ray interactions Photoelectric effect Compton effect The relative contribution of the two effects depends upon the energy and the atomic number of the material Therefore, the attenuation coefficients of different materials have different trends as a function of energy

47 Coherent

48 Dual-Energy Radiography

49 Dual-E Example μ f t f The attenuation of the two materials is given by μ g ( μ ) t f t f +μ g tg g I = I e a o

50 Dual-E Example μ f t f We can define a quantity, T, such that μ g t g T 18 = μ f t f + μ g t g and T 40 = μ f t f + μ g t g at 18 kev at 40 kev

51 Dual-E Example μ f μ g t f t g Using data from Johns and Yaffe (1987) for fat and glandular tissue gives T 18 = 0.6t f + 1.0t g at 18 kev and T 40 = 0.2t f + 0.3t g at 40 kev

52 μ f μ g t f t g Dual-E Example If you multiply T 40 by 4, and subtract T 18, you get T sub = (4* )t f + (4* )t g = 0.2 (t f + t g ). Now, fat and glandular tissue have the same attenuation, and thus they lack contrast

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54 Energy Subtraction In energy subtraction, contrast media is injected first Then, a series of sequential image pairs is obtained Each image pair consists of one high energy and one low energy image Images are then processed and subtracted pair-wise

55 Energy Subtraction Low High Time

56 Dual-Energy Contrast- High Energy Enhanced Imaging Low Energy High Energy Low Energy SI DE ( x, y) = ln( SI ( x, y)) w ln( SI ( x, y)) H t L

57 Lewin et al. CE DSM was performed on 26 subjects with mammographic or clinical findings warranting biopsy. High-energy (44-49 kvp, + 8mm Al filtration) and lowenergy (30-33 kvp) images were obtained pair-wise, following administration of iodinated contrast. A weighted logarithmic subtraction of the images was performed to obtain images that preferentially show iodine. 13 subjects had invasive cancers, 11 of which enhanced strongly, 1 moderately and 1 weakly. 1 case of DCIS demonstrated a weak enhancement In the 12 benign cases, 2 enhanced diffusely and 2 enhanced weakly focally. JM Lewin et al., Radiology 228: , 2003.

58 Two-View Film Mammogram (wire on excisional biopsy scar) (cyst)

59 Lateral... Sagittal Post-contrast MRI to Medial

60 Post-Contrast Dual-Energy Digital Subtraction Mammography

61 XCounter Mammo-3T Prototype

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68 DE-DBT: Patient 1 Age: 55 Diagnosis: Invasive ductal carcinoma Sign: mass in axillary tail region

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71 Dual Energy Imaging Subtraction of images increases noise, and does not alter intrinsic subject contrast However, subtraction reduces background structure, increasing conspicuity of residual signals Dual energy imaging is sensitive to scatter and beam hardening Subtraction works best for large objects where the residual signals and noise are distinguishable.

72 Iodine HE Stepwedge Images Not corrected Corrected

73 Corrected Iodine SI 4 mg I/cm2 2 mg I/cm2 0.5 mg I/cm2 1 mg I/cm2 10 mg I/cm2 Not corrected 4 mg I/cm2 2 mg I/cm2 1 mg I/cm2 0.5 mg I/cm2 10 mg I/cm2 20 mg I/cm2 10 mg I/cm2 20 mg I/cm2

74 Iodine HE Stepwedge Images Radius: 70 Not corrected Corrected Proj images, angle 1, W/Cu,49 kv, 100mAs w/sn, 45kV, 100 mas Total Thickness: 25 mm iodine phantom + 40 mm stepwedge

75 Quantification of Glandularity and Iodine uptake 100% Ad 2 mg I/cm2 100% Gl 10 mg I/cm2 23 degrees Corrected

76 Energy Subtraction Advantages: Motion artifacts are rare Disadvantages: System modifications are necessary to allow rapid change of filter material and kvp Detector must be suited to rapid readout Poorer separation of tissue and contrast agent Beam hardening artifacts

77 Molecular Imaging Molecular Imaging in a broad sense implies visualizing normal and abnormal cellular functions by utilizing either biochemical or pharmacological probes. Ideally, the imaging technique should not perturb the function which is being assessed.

78 Molecular Imaging Molecular Imaging in a broad sense implies visualizing normal and abnormal cellular functions by utilizing either biochemical or pharmacological probes. Ideally, the imaging technique should not perturb the function which is being assessed.

79 Molecular imaging in intact species: methods and agents Sensitivity pm Modality Agents H R Primary uses Examples Optical FMT fluorescent proteins X gene expression, tagging superficial structures BLI luciferin X gene expression, therapeutic monitoring GFP, RFP, NIRF probes fluc rluc nm Nuclear SPECT 99m Tc, 123/5 I, 111 In X X site-selectivity, protein labeling 99m Tc-annex in V, 123 I- A85380 PET 11 C, 18 F, 124 I, 64/62/60 Cu X X site-selectivity, gene expression, drug dev mnt 11 C-RAC, 124 I-FIAU, 64 Cu-ATSM μm MRI Spectroscopy Contrast agents endogenous metabolites X X CNS, prostate, heart, breast NAA, Cr, Cho, Glx, mi, 31 P Gd, Mn, FeO X cell trafficking, enzymatic activation poly-l-lysine, dendrimers, MION μm X-ray contrast agents Iodine, Au Nanoparticles X Cancer Gold Nanoparticles (10 μm) Ultrasound contrast agents perfluorinated microbubbles H=human, R=rodent X drug-delivery, gene transfection human albumin (Optison)

80 Nanoparticles Nanoparticles are small polymeric colloidal particles with a therapeutic and/or imaging agent(s) either dispersed in polymer matrix or encapsulated in polymer. Sahoo SK. Labhasetwar V. Nanotech approaches to drug delivery and imaging Drug Discovery Today. 8: , 2003

81 Liposome-encapsulated iodine Karathanasis, et al., Radiology 250(2), 398, 2009

82 In vivo cancer targeting and imaging with semiconductor quantum dots, XH Gao, YY Cui, et al., Nature Biotech, advanced online publication 18 July 2004 Gold NP Tumors are targeted passively by virtue of the leaky tumor vasculature and actively by high affinity binding of NP-antibody conjugates to tumor antigens

83 At mammographic energies, ten 100nm gold nanoparticles/cell will result in 5% subject contrast. Alexander G. Tkachenko, J. AM. CHEM. SOC. 2003, 125,

84 Summary Contrast-enhanced digital breast tomosynthesis is possible using either temporal subtraction or energy subtraction. Early clinical results indicate that CE DBT gives clinical results which are concordant with MRI. Technical challenges still exist before CE DBT will be widely available.